We have determined the structure of the human U1 snRNA promoter by microinjection of several mutant U1 templates into Xenopus laevis oocytes. These deletion templates were assayed for their ability to express mature U1 RNA and for their ability to compete for limiting transcription factors. We have mapped five separate regions, called promoter elements A, B, C, D, and E. Element A, located between positions -8 and -50, stimulates transcription 3- to 5-fold increases the accuracy of initiation; element B (between -50 and -80) fixes the site of initiation and stimulates transcription greater than 100-fold; element C (upstream of -129) increases the efficiency of element B 3- to 5-fold; element D (between -191 and -231) is an orientation-independent and partially position-independent enhancer responsible for a 100-fold stimulation of transcription; element E (between -335 and -393) increases the ability to compete with other snRNA genes 4-fold. All five promoter elements are required for effective competition with the wild-type U1 promoter suggesting that binding of transcription factor(s) to the complex is cooperative. The U1 RNA and some mRNA gene transcription complexes appear to share one or more transcription factors.

Animals↗

PubMed1987

[Breast cancer in young women with a history of breast cancer in their mother].

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Adolescent↗

PubMed1987

Respiratory dysfunction after potroom asthma.

Thirty-five men developed bronchial asthma while working in the potrooms in a primary aluminum production plant. Their asthma was diagnosed as work-related ("potroom asthma"). When examined 1-43 months after cessation of exposure (average follow-up period 2.5 yr), the group had an increased relative risk of morning cough (RR 1.7 CL95% 0.6-5.1), dyspnea on exertion (RR 2.8 CL95% 0.9-8.4), and wheezing (RR 6.1 CL95% 2.3-16.3) compared to controls from the same plant, in a 1:2 matched analysis. Matching criteria were age, smoking habits, and time of employment in the plant. The group means for FEV1 and MMEF were lower than for the controls, but the differences were not statistically significant. Ten of the 35 reported persisting asthma, dyspnea at night, or dyspnea on exertion. The study indicates an increased risk of respiratory dysfunction after potroom asthma. Medical follow-up after cessation of exposure is recommended.

Aluminum↗

PubMed1987

Structure and expression of U-snRNA genes.

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Animals↗

PubMed1987

Is growing old a disease? A study of the attitudes of elderly people to physical symptoms.

In a survey of people living at home, aged 77 years and over, a total of 126 women and 77 men were interviewed concerning their attitudes to their physical symptoms. For each organ system the subjects indicated whether their symptoms were considered to be a normal condition for elderly people or a manifestation of a disease. To a large extent symptoms were accepted as a normal condition, however, a highly significant difference in their attitudes to symptoms stemming from different systems was found (p less than 0.001). Generally, compared with severe symptoms, mild symptoms were accepted more readily as a normal condition in old age. Although most of the elderly people had seen a doctor because of their symptoms, a highly significant difference was found in consultation rates among elderly persons with symptoms from different organ systems (p less than 0.001). The attitudes to symptoms influenced the tendency of the subjects to consult a doctor (p less than 0.05). The need for education of elderly people and health professionals is discussed.

Aged↗

PubMed1987

Survival of large bowel carcinoma patients with different DNA ploidy.

One hundred patients operated for large bowel carcinoma were divided into a distinct aneuploid group of 63, and a near diploid one of 37. Flow cytometry was used for determination of the DNA ploidy pattern. All tumours in the aneuploid group contained one or more aneuploid cell populations. All patients were followed clinically from 3.5 to 7.8 years. The corrected 5 year survival was 64% and 49% for patients with near diploid and aneuploid tumours, respectively (not significant). Significant differences in corrected survival time were not observed for Dukes' stages A, B, and C patients pooled, nor for Dukes' stage D patients. However, for Dukes' stage C patients alone, there was a tendency (P = 0.10) for patients with near diploid tumours to show a better survival. A highly significant predominance of aneuploid tumours was seen in males, in contrast to an equal distribution of aneuploid and near diploid tumours in females. A slight predominance of aneuploid tumours in the left colon and rectum was seen. Both these findings indicate the influence of environmental factors (hormonal, anatomical, phenotypical) on the development of tumours with a particular DNA ploidy pattern.

Adult↗

PubMed1987

Differential accumulation of U1 and U4 small nuclear RNAs during Xenopus development.

We showed previously that those U1 small nuclear RNA (snRNA) genes of Xenopus laevis which are transcribed very actively in early embryos are quiescent in mature (stage VI) oocytes (Forbes et al. 1984). Although that study demonstrated that differential control of snRNA genes occurred, it did not describe snRNA accumulation during development. Using high-resolution polyacrylamide gels in combination with Northern blot hybridization and RNA sequence analyses, we show here that Xenopus has at least three classes of U1 and U4 snRNAs that are distinguishable by their differential expression of oocytes, embryos, tadpoles, and frogs. Adult snRNAs appear to be synthesized constitutively throughout Xenopus development and comprise the major species in tissues from large tadpoles and frogs. Embryonic snRNAs are the principal species accumulating during the two periods of rapid snRNA synthesis, i.e., in previtellogenic oocytes and early embryos. Tadpole RNAs are minor species that are most prominent in young feeding tadpoles. Transcription of both embryonic and adult snRNA genes is activated at the midblastula transition (MBT), but expression of the embryonic genes is switched off selectively within a few days after MBT. Although the precise timing of this inactivation differs significantly for U1 and U4 genes, the overall pattern of differential expression is common to U1 and U2 snRNA genes. Because of sequence differences between the snRNAs accumulating at various stages, the resulting populations of snRNPs could have different splice-site specificities leading to altered patterns of pre-mRNA splicing during development.

Animals↗

PubMed1987

The transcription of Xenopus laevis embryonic U1 snRNA genes changes when oocytes mature into eggs.

X. laevis stage VI oocytes respond differently from unfertilized eggs when injected with the genes for X. laevis embryonic U1 RNAs, xU1b1, and xU1b2. Upon maturation of oocytes into eggs, the efficiency of transcription decreases greatly and the ratio of xU1b1 to xU1b2 RNA transcription changes. Moreover, DNA replication is now required for transcription. Because of differences in the 5'-flanking regions of the two xU1b genes, xU1b2 RNA transcription predominates after injection into oocytes; in contrast, xU1b1 RNA transcription predominates after injection into unfertilized eggs. Our results also indicate that in oocytes a factor that interacts with sequences close to the coding region is limiting, whereas in eggs a factor that recognizes far-upstream sequences required for enhancer activity is limiting. Qualitatively, expression of the embryonic xU1b genes injected into eggs closely resembles that of the endogenous genes during early embryogenesis.

Animals↗

PubMed1987

Continuous subcutaneous pump infusion of somatostatin analogue SMS 201-995 versus subcutaneous injection schedule in acromegalic patients.

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 micrograms/24 h. Subcutaneous injections (33 micrograms) induced impressive suppression of serum GH lasting 3-6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 ng/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4-102 ng/ml) implying either that adequate suppression by the SMS 201-995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201-995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201-995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin-C immunoreactivity (all patients) decreased from 496 +/- 129 (mean +/- SD) to 385 +/- 100 ng/ml (P less than 0.003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 +/- 76 ng/ml). The normal adult mean is 179 +/- 40 ng/ml. Computer tomographic (CT) scans of the sellar region were performed in all patients before and after the experimental week. Two patients had extracellular tumours whose size decreased from 8.2 to 4.1 cm3 and from 12.6 to 10.5 cm3. The results demonstrate that superior and stable suppression of GH secretion is obtained during continuous s.c. pump infusion of SMS 201-995.

Acromegaly↗

PubMed1987

Use of social and health services by elderly people during the terminal 18 months of life.

In a randomised and controlled intervention study elderly people aged 75 or more were visited regularly in their own homes over a period of three years. An age and sex matched control group was not contacted until the conclusion of the study period. In the present study, the use of social and health services during the terminal 18 months of life was computed for each individual member of the study group. The categories of services included the bed usage in hospitals, the stays in nursing homes, the provisions of home help and home nursing care as well as contacts with general practitioners. No differences in the use of social and health services were found between the visited elderly (n = 25) and the control group (n = 46). About 50% of the elderly had a considerable use of public services during the months prior to death, and only 14% received no public support, disregarding the terminal phase. Among those elderly people belonging to the study group, and who died within the study period, an increased use of the above mentioned services was seen during all 18 months. However, an increased use of hospital beds was only computed during the terminal 6 months of life. 58% of the bed days were used for patients who died during the next few months.

Aged↗

PubMed1987

Prodromal immune manifestations in EMC-M virus induced diabetes: islet bound and circulating antibodies, and changes in lymphocyte subsets.

The thymus-dependence of the encephalomyocarditis (EMC-M) virus induced diabetes has been demonstrated in comparative studies of normal and immunodeficient mice. Since the lymphocytic infiltration in the islets of Langerhans is modest during the virus infection, we have looked for possible indications of humoral immune mechanisms. Using fluorescence microscopy the presence of immunoglobulins in the islets could be shown 3 days after EMC-M-virus inoculation, gradually disappearing about day 14. The Ig deposit is scattered throughout the islets, but the precise target of Ig's has not been detected. Circulating islet cell surface reactive antibodies were demonstrable from the fourth day until about the third week. This period coincides largely with the period in which Ig deposits were present. Virus antibodies in peripheral blood could not be detected until the fifth day after the virus inoculation, whereas virus could be isolated from the third day. Beginning from day 5, about one third of the mice developed severe hyperglycaemia with blood glucose levels up to 35 mmol/l. Lymphocyte subsets of spleen cells were measured using a fluorescence activated cell sorter. Six days after virus inoculation the mean percentage of Lyt 2-positive (suppressor/cytotoxic) cells decreased below the value for control mice (p less than 0.05), but increased significantly (p less than 0.02) 2 weeks later.

Animals↗

PubMed1987

Isodense middle fossa arachnoid cyst and subdural hematoma: a diagnostic problem on CT.

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Adolescent↗

PubMed1987

Astrocytes in the postnatal central nervous system. From birth to 14 years of age. An immunohistochemical study on paraffin-embedded material.

The postnatal development of the fibrillary astrocyte in 25 children without any anamnestic or post mortem signs of disease were studied. The investigation was performed on basis of the immunoperoxidase method for glial fibrillary acidic protein (GFAP). The supporting function of the external glial limiting membrane, the glial vascular limiting membrane and the metabolic role of the astrocytes are stressed. During the postnatal myelination of the white matter the immature astrocyte changed into the mature form and a dense fibrous network developed. The radially oriented glial processes of the Bergmann astrocytes of the cerebellum guided the fetal external granular cells during the migration. In the brainstem we found minor variations of the dense fibrous astrocytic network both in children dead after accidents and in sudden infant death syndrome. These findings presumably demonstrate a normal pattern.

Adolescent↗